The hypothesis is developed that myocardial fibrillation stems from variable decoupling of individual myocardial cells and their reversion to intrinsic spontaneous activity. Tissue culture models are described consisting of spheroidal aggregates or multilayer disc-sheets of coupled embryonic heart cells which normally exhibit an entrained rhythmic beat. Methods are outlined whereby fibrillation can be induced at will in these preparations by experimental manipulation. Experiments are proposed in which the degree of electrical coupling among cells will be measured directly during normal synchronous beating and while cells are engaged in arrhythmic and fibrillatory activity, to test the hypothesis and to derive information about the properties of the transcellular conduction channels. Coupling will be assessed in terms of beat synchronization, passage of fluorescent dyes, passage of current pulses, and cross-correlation of membrane noise. The last is a wholly novel approach which also yields information regarding the elemental electrical properties of cardiac membrane conductance channels. Ultrastructural changes in junctional membranes will be examined in relation to the formation, separation, and breakdown of gap junctions during coupling and decoupling, and this information will be correlated with results from the electrical studies. Similar experiments will be performed for comparison on intact mammalian atrial preparations. BIBLIOGRAPHIC REFERENCES: DeHaan, R.L. (1976) Cell coupling and electrophysiological differentiation of embryonic heart cells. In Tests of Teratogenicity in Vitro (ed M. Marois). Nathan, R.D., J. Pooler and R.L. DeHaan. (1976) Ultraviolet-induced alterations in beat-rate and electrical properties of embryonic chick heart cell aggregates. J.Gen. Physiol.